Exogenous IL-12 and its effect on TH1/TH2 cell activity after cardiac surgery

There is controversy about the origin of the alterations in T helper 1 (TH1)/TH2 cell activity after major surgical procedures such as on-pump cardiac surgery. We hypothesized that a postoperative decrease in interferon (IFN) gamma-producing TH1 lymphocyte activity may be the sole cause of this TH1/TH2 shift and that the addition of recombinant IL-12 can reverse TH1 suppression. Peripheral blood mononuclear cell fractions from 20 low-risk elective cardiac surgery patients were analyzed preoperatively (d0) and on the first (d1), third (d3), and sixth (d6) postoperative days. We determined the absolute numbers of T helper lymphocytes, IFN-gamma-producing TH1 cells, and IL-4-producing TH2 cells after stimulation and measured IFN-gamma and IL-4 levels in the supernatants of stimulated peripheral blood mononuclear cell cultures, absolute monocyte counts, human leukocyte antigen-DR expression, and intracellular IL-12 synthesis under comparable conditions. Recombinant IL-12 alone or in combination with a neutralizing antibody was added. T helper lymphocyte counts were reduced postoperatively from d1 to d6 (P < 0.05). Absolute IFN-gamma- and IL-4-positive T helper lymphocyte counts were reduced on d1 (P < 0.05). Intracellular IL-4 production in T helper lymphocytes remained postoperatively unchanged. Interferon gamma synthesis was significantly reduced until d3 (P = 0.001) and significantly increased after IL-12 addition (P < 0.05). This effect was reversed by the addition of a neutralizing anti-IL-12 antibody. The TH1/TH2 shift after cardiac surgery seems to be caused primarily by a decrease in cellular IFN-gamma synthesis in TH1 lymphocytes. Because TH1 suppression can be reversed by IL-12, it is more likely to be the result of altered stimulation pathways than cellular defects.